Location: Infectious Bacterial Diseases ResearchTitle: Host responses to mycobacterial infections: Spotlight on biomarker discovery to predict vaccine Author
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/20/2014
Publication Date: 6/16/2014
Citation: Vordermeier, H.M., Buddle, B.M., Waters, W.R., Villarreal-Ramos, B., Golby, P., Aranday-Cortes, E., Hogarth, P.J., Hewinson, R.G. 2014. Host responses to mycobacterial infections: Spotlight on biomarker discovery to predict vaccine [abstract]. Abstract No. 10. Interpretive Summary:
Technical Abstract: The global spread of tuberculosis (TB) in animals and humans result in enormous economic. social and public health burdens. TB vaccine development in both humans and animals has produced a growing portfolio of candidates with potential applicability across species. However, the lack of understanding of the underlying biological mechanisms and the lack of correlates of protection that can guide vaccine design or animal experiments, or that can be used as a credible endpoint in field trials are hampering progress. The bottleneck for cattle vaccine development is the expense and paucity of BL3 facilities. Reliable gating criteria to select only the most promising vaccine candidates for testing in BL3 experimentation or field trials would greatly accelerate the pace of vaccine development. Hence, significant research efforts have been directed towards develop and validate such biomarkers using hypothesis - as well as data-driven approaches including host transcriptome and proteome analysis combined with a systems biology philosophy. Vaccination outcome based on relevant clinical endpoints allows the classification of vaccinated cattle in those that were successfully vaccinated, and those in that vaccination was unsuccessful. This is a powerful way of stratifying data to identify biomarkers that predict vaccine efficacy (i.e. those that be measured post-vaccination but without the need for M. bovis challenge), markers that correlate with protective immunity (i.e. those that can be measured after M. bovis infection that will give insights into the nature of protective immunity), or markers that correlate with disease progression (measured after challenge that can serve also as inverse correlate of protection as these markers are generally of lower magnitude in successfully vaccinated animals post-challenge). I will present an update on the significant progress that has been made in the discovery of such biomarkers as well as discuss how these markers can be used to extend our understanding of the fundamental processes underlying the host responses against bovine tuberculosis, both protective and immune pathogenic.